子宮体癌（漿液性腺癌）の遺伝子変異とコピー数変異：PNAS

当ブログで好む遺伝子変異とコピー数変異の子宮体癌版である。Yale大学から。下の表がすべて。

ちなみにここでの子宮体癌は漿液性腺癌であり、日本では極めて少ない予後の悪いサブカテゴリーだそうな。ちなみに欧米では10%.　52症例集めて解析であるからご苦労さまである。

• 子宮体癌取扱い規約(日産婦1995)に従えば,子宮体部に発生する上皮性腫瘍のうち悪 性腫瘍すなわち癌として分類されるものが子宮内膜癌(endometrial carcinoma)と呼ばれ,子宮内膜癌は

1. 類内膜癌(endometrioid carcinoma)----------------93.8%
2. 漿液性腺癌(serous adenocarcinoma)--------------2.41%
3. 明細胞腺癌(clear cell adenocarcinoma),
4. 粘液性腺癌(mucinous adenocarcinoma),
5. 扁平上皮癌(squamous cell carcinoma),
6. 混合癌(mixed carcinoma),
7. 未分化癌(undifferentiated carcinoma)に分類される.

• さらに類内膜癌は類内膜腺癌(endometrioid adenocarcinoma)と扁平上皮への分化を伴う類内膜腺癌(endometrioid adenocarcinoma with squamous differentiation)に分類されている.
• 本分類に従って1993年から2002年までの日本産科婦人科学会婦人科腫瘍委員会に報告され た子宮内膜癌症例の合計25,214例を再分類したところ,本邦の子宮内膜癌の大半を類内膜癌が占めており(93.8%),漿液性腺癌,明細胞腺癌,粘液性腺癌,扁平上皮癌,その他の組織型の占める割合はそれぞれ2.41%,1.12%,1.07%,0.30%,1.26%であった. このように,わが国の子宮内膜癌に占める漿液性腺癌,明細胞腺癌の割合は決して多くはない反面,近年増加傾向が窺われる.欧米では漿液性腺癌が10%前後, 明細胞腺癌が2~3%前後を占めるとされているので,わが国における子宮内膜癌の組織 型の比率はこれに近づきつつあるといえよう.また,漿液性腺癌や明細胞腺癌は類内膜癌 に比して予後不良とされている.したがって,これらの治療に当たる場合に類内膜癌とは 差別化した戦略を立てることが可能か否か,現時点で検討しておくことは有用と考えられる.
• 予後は悪い

 以上 日産婦誌58巻9号より引用


PNAS 2013 110 (8) 2916-2921; published ahead of print January 28, 2013,

Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma 

Siming Zhao,Murim Choi, John D. Overton, and Alessandro D. Santin

Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations. The mutations in these latter tumors showed hallmarks of defects in DNA mismatch repair. Among the remainder, we found a significantly increased burden ofmutation in 14 genes. In addition to well-known cancer genes (i.e., TP53, PIK3CA, PPP2R1A, KRAS, FBXW7), there were frequent mutations in CHD4/Mi2b, a member of the NuRD–chromatin-remodeling complex, and TAF1, an element of the core TFIID transcriptional machinery. Additionally, somatic copy-number variation was found to play an important role inUSC, with 13 copy-number gains and 12 copy-number losses that occurred more often than expected by chance. In addition to loss of TP53, we found frequent deletion of a small segment of chromosome 19 containing MBD3, also a member of the NuRD–chromatin-modification complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (an upstream activator of PIK3CA), and CCNE1 (a target of FBXW7-mediated ubiquitination). These findings identify frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer.

Fig. 5. Major altered pathways in USC. The altered percentages shown for genes and pathways come from the 25 matched tumors with CNV information.Genes are colored based on their activity in the pathway diagram. Pink, predicted activated; blue, predicted inactivated; gray, uncertain at this stage; lines with blunt end, inhibiting effect; lines with pointed end, promoting effect; dotted line, uncertain. Mutation and CNV status for each gene across the 25samples are shown at the bottom following the pathway diagram.